tbuckley/cabot-search huggingface dataset:
Completion of electronic patient reported outcome measures among diverse cancer patients treated in an integrated health system.
Authors: Eric Adjei Boakye, Samantha Tam, Theresa Zatirka, Christine Neslund-Dudas, Wan-Ting Su, Cara E Cannella, Steven S. Chang, Benjamin Movsas
Journal: Journal of Clinical Oncology (2022)

e24035 Background: Patient reported outcome measures (PROMs) are derived entirely from patients’ perspectives and complementary to traditional clinical assessment. Use of PROMs as a symptom communication tool has been demonstrated to improve quality of life, decrease health care utilization, and improve overall survival in clinical trial settings. However, clinical trial enrollment is known to be biased, often excluding those with the most difficulty accessing care. Henry Ford Cancer Institute has implemented a PROMs platform integrated with routine clinical care throughout the vertically integrated health system for all cancer disease sites. The purpose of this study is to compare patient characteristics in those responding to and those without response to PROMs to understand potential disparities. Methods: All patients with a diagnosis of cancer and a visit with an oncologic provider were offered an opportunity to complete PROMs between September 16, 2020 to July 19, 2021. Domain-specific National Institute of Health’s computer adaptive technology Patients-Reported Outcomes Measurement Information System (PROMIS) instruments in pain interference, physical function, fatigue, and depression were offered prior to a visit using a patient-facing electronic portal or via iPAD at the time of visit. Patient level demographic, insurance, ZIP code level socioeconomic status and clinical data were compared across PROMs responders and non-responders using multivariable logistic regression. Results: A total of 3,226 patients were included in the study, of whom 1,652 (51.2%) responded to PROMs. The mean age of the patients was 60 years (SD = 13) and 60.5% were females. Most were of white race (68.8%) and were married (56.1%). There was similar distribution of patients with private (43.7%) and Medicare (41.6%) insurance. After adjusting for age, sex, race, marital status, education, income, insurance and stage, patients who were single (aOR = 0.78; 95% CI: 0.65—0.94) or had Medicare insurance (aOR = 0.68; 95% CI: 0.55—0.83) were less likely to respond to the PROMs. Patients diagnosed with early-stage (stages 0,1,2) disease (aOR = 0.79; 95% CI: 0.67—0.93) were less likely to respond to PROMs, but those with unknown stage (aOR = 1.27; 95% CI: 1.04—1.56) were more likely to respond to PROMs compared to those diagnosed with late-stage (stages 3,4) disease. There was no significant association between race and PROMs response. Conclusions: Patients who are single, have Medicare insurance, and early-stage disease are less likely to respond to PROMs. Future implementation efforts need to focus on these populations to ensure equitable availability of PROMs as a tool for symptom communications in patients with cancer.
INSP-02. WHO 2021 classification of CNS tumors
Authors: Pieter Wesseling
Journal: Neuro-Oncology (2022)

Abstract In line with recommendations of the cIMPACT-NOW consortium, the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5 classification) is substantially different from the previous (revised 4th) edition. Salient changes include the separation of pediatric-type low- and high-grade diffuse gliomas from adult-type diffuse gliomas, refinement of the classification of ependymal tumors, and the addition of a newly recognized embryonal CNS tumors. Furthermore, for some tumors the name was changed. For example, diffuse midline glioma (DMG), H3K27M-mutant is now DMG, H3K27-altered (because there are H3-wildtype DMGs that do show loss of nuclear H3K27me3 staining and with a similar prognosis as DMGs, H3K27M-mutant), and supratentorial ependymoma, RELA fusion-positive was changed into ZFTA fusion-positive (as ZFTA (‘zinc finger translocation associated’, the new name for c11orf95) is the more frequent fusion partner in these tumors). The WHO CNS5 tumor classification certainly is an improvement, but it brings several (new) challenges as well. For example, for more CNS tumors it is now impossible to reach a state-of-the-art ‘histomolecular’ diagnosis in case molecular tools for assessment of essential diagnostic characteristics are not available. In those situations, adding NOS (not otherwise specified) to the histology-based diagnosis is the way to go. Furthermore, designing the optimal therapeutic management for newly defined tumor types is challenging. And while a more precise classification facilitates enrollment of more homogeneous populations of patients in clinical studies, the higher granularity of CNS tumor taxonomy makes it more difficult to perform studies on a large number of patients for particular tumor types. Still, one would like to think that patients suffering from a CNS tumor are better served by a more precise diagnosis because this allows for a better estimation of prognosis and, hopefully sooner than later, for a more tailored and effective therapeutic approach.
A Programmable <i>In Vivo</i> CRISPR Activation Model Elucidates the Oncogenic and Immunosuppressive Functions of MYC in Lung Adenocarcinoma
Authors: Fredrik I. Thege, Dhwani N. Rupani, Bhargavi Brahmendra Barathi, Sara L. Manning, Anirban Maitra, Andrew D. Rhim, Sonja M. Wörmann
Journal: Cancer Research (2022)

Conventional genetically engineered mouse models (GEMM) are time-consuming, laborious, and offer limited spatiotemporal control. Here, we describe the development of a streamlined platform for in vivo gene activation using CRISPR activation (CRISPRa) technology. Unlike conventional GEMMs, this model system allows for flexible, sustained, and timed activation of one or more target genes using single or pooled lentiviral guides. Myc and Yap1 were used as model oncogenes to demonstrate gene activation in primary pancreatic organoid cultures in vitro and enhanced tumorigenic potential in Myc-activated organoids when transplanted orthotopically in vivo. Implementation of this model as an autochthonous lung cancer model showed that transduction-mediated activation of Myc led to accelerated tumor progression and significantly reduced overall survival relative to nontargeted tumor controls. Furthermore, Myc activation led to the acquisition of an immune suppressive, “cold” tumor microenvironment. Cross-species validation of these results using publicly available RNA/DNA-seq datasets linked MYC to a previously described immunosuppressive molecular subtype in patient tumors, thus identifying a patient cohort that may benefit from combined MYC- and immune-targeted therapies. Overall, this work demonstrates how CRISPRa can be used for rapid functional validation of putative oncogenes and may allow for the identification and evaluation of potential metastatic and oncogenic drivers through competitive screening. Significance: A streamlined platform for programmable CRISPR gene activation enables rapid evaluation and functional validation of putative oncogenes in vivo.
Genetic correlates of phenotypic heterogeneity in autism
Authors: Varun Warrier, Xinhe Zhang, Patrick Reed, Alexandra Havdahl, Tyler M. Moore, Freddy Cliquet, Claire S. Leblond, Thomas Rolland, Anders Rosengren, Antonia San Jose Caceres, Hannah Hayward, Daisy Crawley, Jessica Faulkner, Jessica Sabet, Claire Ellis, Bethany Oakley, Eva Loth, Tony Charman, Declan Murphy, Rosemary Holt, Jack Waldman, Jessica Upadhyay, Nicola Gunby, Meng-Chuan Lai, Gwilym Renouf, Amber Ruigrok, Emily Taylor, Hisham Ziauddeen, Julia Deakin, Sara Ambrosino di Bruttopilo, Sarai van Dijk, Yvonne Rijks, Tabitha Koops, Miriam Douma, Alyssia Spaan, Iris Selten, Maarten Steffers, Anna Ver Loren van Themaat, Nico Bast, Sarah Baumeister, Larry O’Dwyer, Carsten Bours, Annika Rausch, Daniel von Rhein, Ineke Cornelissen, Yvette de Bruin, Maartje Graauwmans, Elzbieta Kostrzewa, Elodie Cauvet, Kristiina Tammimies, Rouslan Sitnikow, Guillaume Dumas, Yang-Min Kim, Thomas Bourgeron, David M. Hougaard, Jonas Bybjerg-Grauholm, Thomas Werge, Preben Bo Mortensen, Ole Mors, Merete Nordentoft, Dwaipayan Adhya, Armandina Alamanza, Carrie Allison, Isabelle Garvey, Tracey Parsons, Paula Smith, Alex Tsompanidis, Graham J. Burton, Alexander E. P. Heazell, Lidia V. Gabis, Tal Biron-Shental, Madeline A. Lancaster, Deepak P. Srivastava, Jonathan Mill, David H. Rowitch, Matthew E. Hurles, Daniel H. Geschwind, Anders D. Børglum, Elise B. Robinson, Jakob Grove, Hilary C. Martin, Thomas Bourgeron, Simon Baron-Cohen
Journal: Nature Genetics (2022)

The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (n
Does perceived stigma or shame affect stage of presentation in Iraqi Kurdish women diagnosed with breast cancer?
Authors: Anees B. Chagpar, Suzann Qader, Mehdi Baqri, Kaveh Khoshnood, Hamdia Ahmed
Journal: Journal of Clinical Oncology (2022)

e18680 Background: The concept of breast cancer related stigma and its effect on stage at presentation has been understudied in the Iraqi context. We sought to determine the extent to which perceived stigma or shame affected stage at presentation in Iraqi women diagnosed with breast cancer. Methods: A survey was conducted of 100 cancer patients seen at the Breast Center in Erbil, Kurdistan. Patients were asked subjectively whether they felt a sense of shame with the diagnosis of breast cancer and whether this delayed them in being diagnosed. In addition, a breast cancer stigma scale (BCSS) that has been validated in Arab women was fielded, and objective data regarding stage at presentation was collected. The BCSS has a possible score of 12-60, with lower scores indicating higher levels of stigma. Results: : Of the 100 women surveyed; only 7% were diagnosed at stage 1. While only 6% of women stated that they felt shame when diagnosed with breast cancer, 48% felt that some sense of shame delayed them getting diagnosed. The median BCSS score was 43 (range; 16-60). While marital status (p = 0.360), rural vs. urban setting (p = 0.380), working outside the home (p = 0.669), educational level (p = 0.203) and monthly household income (p = 0.642) were not associated with whether women presented with stage 1 breast cancer at diagnosis, there was a trend towards higher BCSS among those with stage 1 disease (p = 0.076). Further, patients who reported that feelings of shame either “somewhat” or “very much” delayed them being diagnosed were more likely to present with higher stage disease than those who felt this did “not at all” cause a delay (100% vs. 87.8%, p = 0.016). Indeed, all six patients diagnosed with stage 1 disease reported that feelings of shame did “not at all” delay them from being diagnosed. Conclusions: Most patients in the Iraqi Kurdistan context are diagnosed with later stage disease. Feelings of stigma or shame may contribute to later diagnosis in this context.
Transurethral ultrasound ablation (TULSA) for benign prostatic hyperplasia: Three-month clinical outcomes
Authors: A. Viitala, M. Anttinen, P. Doerwald, P. Mäkelä, T. Sainio, I. Virtanen, P. Taimen, R. Blanco Sequeiros, P.J. Boström
Journal: European Urology (2022)
Production of food-grade microcarriers based on by-products from the food industry to facilitate the expansion of bovine skeletal muscle satellite cells for cultured meat production
Authors: R. Christel Andreassen, Sissel Beate Rønning, Nina Therese Solberg, Krister Gjestvang Grønlien, Kenneth Aase Kristoffersen, Vibeke Høst, Svein Olav Kolset, Mona Elisabeth Pedersen
Journal: Biomaterials (2022)

A major challenge for successful cultured meat production is the requirement for large quantities of skeletal muscle satellite cells (MuSCs). Commercial microcarriers (MCs), such as Cytodex®1, enable extensive cell expansion by offering a large surface-to-volume ratio. However, the cell-dissociation step post cell expansion makes the cell expansion less efficient. A solution is using food-grade MCs made of sustainable raw materials that do not require a dissociation step and can be included in the final meat product. This study aimed to produce food-grade MCs from food industry by-products (i.e., turkey collagen and eggshell membrane) and testing their ability to expand bovine MuSCs in spinner flask systems for eight days. The MCs' physical properties were characterized, followed by analyzing the cell adhesion, growth, and metabolic activity. All MCs had an interconnected porous structure. Hybrid MCs composed of eggshell membrane and collagen increased the mechanical hardness and stabilized the buoyancy compared to pure collagen MCs. The MuSCs successively attached and covered the entire surface of all MCs while expressing high cell proliferation, metabolic activity, and low cell cytotoxicity. Cytodex®1 MCs were included in the study. Relative gene expression of skeletal muscle markers showed reduced PAX7 and increased MYF5, which together with augmented proliferation marker MKI67 indicated activated and proliferating MuSCs on all MCs. Furthermore, the expression pattern of cell adhesion receptors (ITGb5 and SDC4) and focal adhesion marker VCL varied between the distinct MCs, indicating different specific cell receptor interactions with the various biomaterials. Altogether, our results demonstrate that these biomaterials are promising prospects to produce custom-fabricated food-grade MCs intended to expand MuSCs.
Efficacy and safety of apatinib in the treatment of advanced platinum-resistant recurrent epithelial ovarian cancer: A retrospective study.
Authors: Zhongmian Pan, Zhongbin Luo, Hongying He, Yujie Chen, Bingbing Zhao, Zhijun Yang, Li Li
Journal: Journal of Clinical Oncology (2022)

e17594 Background: Apatinib is an oral anti-angiogenic drug that mainly targets vascular endothelial growth factor receptor 2 (VEGFR-2) and is widely used in a variety of solid tumours. The purpose of this study is to evaluate the clinical efficacy and safety of apatinib in patients with advanced platinum-resistant relapsed epithelial ovarian cancer (EOC). Methods: This study retrospectively analyzed the clinical data of patients with stage IIIC-IV platinum-resistant relapsed EOC between January 2014 and May 2018. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were reviewed and evaluated. The propensity score matching (PSM) method was used to determine the data included in this study of the final case. Results: This study included 36 patients in the apatinib group and 72 patients in the control group, according to the 1:2 propensity matching. The follow-up ended in January 2019, and the median follow-up time was 28 months. The ORR was 30.56% in the apatinib group and 16.67% in the control group. The DCR in both cohorts was 66.67% and 44.44%, respectively. The median PFS (6.0 vs. 3.3 months) and OS (15.8 vs. 9.2 months) in the apatinib group were significantly longer than that in the control group. In addition, apatinib was more effective than conventional chemotherapy in reducing the risk of PFS [HR 0.40 (95% CI 0.22-0.76), P = 0.0017] and OS [HR 0.40 (95% CI 0.21-0.73), P = 0.002]. Multivariate Cox analysis showed that the course of treatment and decrease in serum CA125 levels are independent risk factors for PFS in patients, while for apatinib, the length of treatment course and the location of the lesion are independent risk factors for recurrence that affects the OS of patients. The most common grade 3/4 toxicities in the apatinib group were hypertension, hand-foot syndrome, and oral mucosal ulcers. Conclusions: Apatinib therapy was an effective treatment for patients with advanced platinum-resistant relapsed EOC. The toxicities were tolerable and manageable.
Renal parenchymal infiltration is the primary determinant of prognosis of patients with non-metastatic clear cell renal cell carcinoma
Authors: H. Tanaka, Y. Fukawa, K. Yamamoto, S. Fukuda, S. Uehara, S. Yoshida, M. Yokoyama, Y. Matsuoka, S.C. Campbell, Y. Fujii
Journal: European Urology (2022)
Changes in circulating tumor DNA (ctDNA) and outcomes in solid tumors treated with immune checkpoint inhibitors (ICIs).
Authors: Laith Al-Showbaki, Marco Iafolla, Faris Tamimi, Consolacion Molto, Abhenil Mittal, David W. Cescon, Eitan Amir
Journal: Journal of Clinical Oncology (2022)

2544 Background: Quantification of ctDNA levels can be a reliable prognostic tool in several malignancies. More recently, detection of genomic alterations in ctDNA have been validated as a predictive biomarker to guide treatment planning. Dynamic changes in ctDNA levels over time and in response to treatment may also provide prognostic information. However, less is known about the value of changes to ctDNA levels in response to immune checkpoint inhibitors (ICIs). Methods: We searched MEDLINE (host:PubMed) and reviewed trials exploring outcomes of patients with advanced solid tumors receiving ICIs in which outcomes were reported based on changes to ctDNA levels. ctDNA clearance was defined as reported in individual trials. Typically, this was defined as either &gt;50% reduction or a reduction to undetectable levels. We extracted progression free survival (PFS) and/or overall survival (OS) values, related 95% Confidence intervals (CI) and/or p-values. Data were then included in a meta-analysis utilizing the generic inverse variance and random effects model. Variation in effect size was examined using random effects meta-regression analysis. Results: A total of 17 trials were included in the meta-analysis; ctDNA levels were detectable in all participants in all studies prior to initiation of ICIs. Method of detection included next generation sequencing and/or droplet digital polymerase chain reaction assays. Overall, low to undetectable ctDNA levels, measured 6-16 weeks after starting treatment was associated with significantly better PFS, (HR 0.20 95% CI, 0.14-0.28; p&lt;0.001). Similarly, OS was superior in patients with substantially reduced or undetectable ctDNA levels after receiving ICIs, (HR 0.18, 95% CI, 0.12-0.26; p&lt;0.001. The results were consistent across all disease sites, lines of treatment, level of change (undetectable vs. &gt;50% reduction) and whether treatment exposure comprised single or multiple ICIs (see Table). Conclusions: In unselected advanced solid tumors, a substantial fall in ctDNA levels in response to ICIs is associated with substantial improvements in both PFS and OS. ctDNA change is an early response biomarker which may allow for de-escalation of cross-sectional imaging in patients receiving ICIs, or support treatment de-escalation strategies. Further research is needed to quantify variations in sensitivity between the available NGS assays, as well as differences discovery range between assay platforms. [Table: see text]
What is driving declines in oncology-prescribed opioids?
Authors: Tarlise Townsend, Magdalena Cerda, Fumiko Chino
Journal: Journal of Clinical Oncology (2022)

6583 Background: Patients with cancer have experienced sharp declines in opioid prescribing during the past decade, raising concerns about insufficient pain management in a population with high rates of undertreated pain. It is unclear whether these declines are driven by certain oncology subspecialties, payors, or clinical guidelines regarding opioid prescribing released in/after March 2016. Methods: We conducted time series analyses using 2006-2019 IQVIA Longitudinal Prescription Data, which represents up to 92% of all U.S. prescription fills. Using log-linear regression stratified by group, we estimated annual percent change in opioid receipt by: subspecialty (medical oncology MO, radiation oncology RO, and surgical oncology SO); payor (third-party; Medicare, including Medicare Part D; Medicaid; cash/out-of-pocket); and pre- versus post-March 2016. Opioid receipt outcomes included: monthly fills of any opioid; monthly fills of extended-release/long-acting (ER/LA) opioids; and monthly number of patients receiving long-term opioid therapy (LTOT). Outcomes were per 1,000 survivors to account for temporal changes in cancer prevalence. Results: Between 2006 and 2019, 14,301,900 opioid fills were prescribed by oncologists to 3,476,354 distinct patients. Across all outcomes, MO had the highest levels of dispensing, followed by RO, then SO; for example, in 2006 MO dispensed 6.2 fills per 1,000 survivors (compared to 1.9 fills among RO, and 0.5 among SO). We observed substantial declines in all opioid outcomes. Per 1,000 survivors, there was an annual decline of: 5.7% (95CI: 5.1-6.3; total unadjusted decline 2006-2019=70.2%) in the rate of all opioid fills; 4.9% (95CI: 4.1-5.6; total unadjusted decline=66.8%) in ER/LA fills; 3.2% (95CI: 1.5-5.0; total unadjusted decline=56.2%) in LTOT fills, and 1.9% in average daily dose (95CI: 1.9-2.0; total unadjusted decline=29.8%). The annual decline in opioid fills prescribed by MO (7.1%, 95CI: 6.6-7.7) was sharper than for RO (5.9%, 95CI: 5.4-6.4) and SO (5.2%, 95CI: 4.7-5.7). Annual declines were steepest among fills paid out-of-pocket (14.5%, 95CI: 13.9-15.0), followed by those paid by Medicaid (13.1%, 95CI: 12.5-13.6), third-party payors (9.3%, 95CI: 8.7-9.9), and Medicare (2.4%, 95CI: 1.8-3.1). Declines in every outcome accelerated following clinical guidelines released in/after 2016. Conclusions: Opioids prescribed by oncologists declined dramatically across groups and outcomes. Medical oncologists were responsible for a disproportionate share of opioid fills in 2006, and for the sharpest declines. Out-of-pocket fills declined more sharply than fills covered by insurance and clinical guidelines may have contributed to accelerating declines. While de-escalation of opioid therapy may reduce risk of opioid-related harms to cancer survivors, care is needed to ensure cancer-related pain is appropriately treated.